BNP and NT-proBNP Interpretation in the Neprilysin Inhibitor Era
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CARDIAC BIOMARKERS (CR DEFILIPPI, SECTION EDITOR)
BNP and NT-proBNP Interpretation in the Neprilysin Inhibitor Era Marco Sbolli 1,2 & Christopher deFilippi 2
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review Describe the mechanisms that may influence change in measured natriuretic peptide levels when using the neprilysin inhibitor sacubitril to treat a patient with heart failure. Recent Findings Prior to the introduction of the neprilysin inhibitor sacubitril as part of a chemical combination with the angiotensin receptor blocker valsartan shown to reduce mortality and heart failure hospitalizations in patients with heart failure with reduced ejection fraction, the natriuretic peptide assays for B-type natriuretic peptide (BNP) and the amino-terminal proBNP (NT-proBNP) assays were shown to have similar diagnostic accuracy to differentiate heart failure from other etiologies of shortness of breath. Sacubitril/valsartan use has been shown to result in a modest and chronic elevation of BNP while reducing levels of NT-prBNP. This review explores the potential impact of these findings on interpreting natriuretic peptide results for diagnosis and prognosis, as well as explore the challenges associated with the heterogeneity of this finding, highlighting the impact of inhibiting neprilysin, a non-specific endopeptidase with multiple target sites within BNP and other proteins. Summary With increased uptake of sacubitril/valsartan expected in patients with heart failure, interpretation of natriuretic peptide assays becomes somewhat more complex, particularly for BNP. However, knowing a baseline steady-state concentration and using the same assay can assist with BNP interpretation for diagnosis and prognosis. Keywords Natriuretic peptide . Neprilysin inhibition . Analytical issue . Assay . Heart failure
Background and Introduction Guidelines recommend natriuretic peptides (NP) as diagnostic and prognostic markers of heart failure since the last decade [1]. The most extensive evidence concerning B-type natriuretic peptide in vitro diagnostic tests was published in the early 2000s. Comparative studies from this era generally demonstrated diagnostic equivalency between measuring the concentration of the active hormone, B-type natriuretic peptide (BNP) versus the amino terminal of the proBNP molecule (NTproBNP). However, the management of heart failure is rapidly
This article is part of the Topical Collection on Cardiac Biomarkers * Christopher deFilippi [email protected] Marco Sbolli [email protected] 1
University of Brescia, Brescia, Italy
2
Inova Heart and Vascular Institute, Fairfax, VA, USA
evolving, and new issues need to be considered when interpreting NPs in the current clinical practice. In 2015, sacubitril/valsartan was approved by the FDA for the reduction of mortality and morbidity in symptomatic heart failure patients with reduced left ventricular ejection fraction (HFrEF). The sacubitril molecule acts via the inhibition of neprilysin, a peptid
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